Numerous approaches are being employed to improve the bone generation and repair cycle (also referred to as the bone repair cascade). Such issues are paramount in the treatment of all bone defects related to degeneration, injury, infection, malignancy, or developmental malformation. One of the approaches is a bone graft procedure. The source of the graft may come from the subject suffering from the bone defect, or so-called autologous bone. Clearly, the use of autologous bone minimizes immunological complications but is accompanied by additional trauma of the subject. Currently, there are several different types of autologous bone graft substitutes that are either currently available or are in various stages of development.
Demineralized bone matrix (DBM) is a manufactured product that has been readily available for over ten years. See for example, Grafton Putty (Osteotech, Eaton-town, N.J.); DBX Putty (MTF [Musculoskeletal Transplant Foundation], available through Synthes, Paoli, Pa.); and AlloMatrix Injectable Putty (Wright Medical Technology, Arlington, Tenn.). DBM is prepared by acid extraction of allograft bone, resulting in loss of most of the mineralized component but retention of collagen and noncollagenous proteins, including growth factors. DBM does not contain osteoprogenitor cells, but the efficacy of a demineralized bone matrix as a bone-graft substitute or extender may be influenced by a number of factors, including the sterilization process, the carrier, the total amount of bone morphogenetic protein (BMP) present, and the ratios of the different BMPs present (Strates et al., (1988) Am J Med Sci, 296:266-9; Urist et al., (1997) Connect Tissue Res, 36:9-20; and Sammarco and Chang, (2002) Foot Ankle Clin, 7:19-41). DBM includes demineralized pieces of cortical bone to expose the osteoinductive proteins contained in the matrix. These activated demineralized bone particles are usually added to a substrate or carrier (e.g. glycerol or a polymer).
Allograft bone is a reasonable graft substitute for autologous bone. It is readily available from cadavers and avoids the surgical complications and subject morbidity associated with harvesting autologous bone. Allograft bone is essentially a load-bearing matrix comprised of cross-linked collagen, hydroxyapatite, and osteoinductive Bone Morphogenetic Proteins (BMP). Human allograft tissue is widely used in orthopedic surgery. Allograft tissue is strong, integrates with the recipient host bone, and can be shaped either by the surgeon to fit the specific defect or shaped commercially by a manufacturing process. Allograft bone is available in two basic forms: cancellous and cortical. Cortical bone is a highly dense structure comprised of triple helix strands of collagen fiber reinforced with hydroxyapatite. The hydroxyapatite component is responsible for the high compressive strength and stiffness of bone while the collagen fiber component contributes to its elastic nature, as well as torsional, shear, and tensile strength. Cortical bone is the main load-bearing component of long bones in the human body.
If the source of the bone graft material is not autologous, a common drawback of bone graft procedures is that the implantation of heterogeneous material into the host bone can initiate an inflammatory response. The inflammatory response is mediated by the production of catabolic cytokines by macrophages that migrate to the allograft surface attempting to remove the foreign body. The purpose of the inflammatory cascade is to promote healing of the damaged tissue, but once the tissue is healed, the inflammatory process does not necessarily end. Left unchecked, this ongoing inflammation can lead to degradation of surrounding tissues and associated chronic pain. Additionally, the inflammation results in delayed allograft incorporation with the host tissue or possibly complete rejection and resorption of the graft. Further, contemporary surgical techniques dealing with treatment of bone defects at or adjacent to the epiphyses of the bones fail to properly promote formation and integration of hylan cartilage.
Accordingly, there is a need for novel compositions and methods leading to improved clinical outcomes of bone grafting.